It is known that desensitization therapy results in a changed immunological response specific for the allergens administered. Such changes are considered to be responsible for the beneficial effects of the treatment and amelioration of the symptoms of allergy.
The immunological changes responsible for benefit are not entirely understood. Although a raised allergen specific IgG antibody response is considered to be a desirable outcome of therapy, it is now believed that certain changes in the allergen specific T cell (i.e., T lymphocyte) response are more important.
Two subclasses of T cell, TH1-like and TH2-like interact with one another via various messenger molecules. In an allergic subject it appears that there is a greater allergen specific TH2 than a TH1 activity. This can lead to a high allergen specific IgE antibody level and greater eosinophil activity. These are two important components of the allergic syndrome.
A change in the above situation to one where there is greater allergen specific TH1 rather than TH2 activity is thought to be an important component of immunotherapy leading to a clinical benefit.
GB-A-1 377 074, corresponding to U.S. Pat. No. 3,792,159, describes a process for preparing coprecipitates of tyrosine having an allergen dispersed therein.
GB-A-1 492 973, corresponding to U.S. Pat. No. 4,070,455, describes a process for preparing coprecipitates of tyrosine having a modified allergen dispersed therein. The allergen is modified by treatment with an agent, such as glutaraldehyde, which causes intra-molecular cross-linking and reduces the allergenicity of the product relative to the unmodified allergen.
3 de-O-acylated monophosphoryl lipid A (hereinafter “3-DMPL” or “MPL”) is known from GB-A-2 220 211, corresponding to U.S. Pat. No. 4,912,094, and assigned to Ribi Immunochem Research, Inc. (Hamilton, Mont.) (“Ribi”). Chemically it is a mixture of 3 de-O-acylated monophosphoryl lipid A with 4, 5, or 6 acylated chains and is manufactured by Ribi. A preferred form of 3 de-O-acylated monophosphoryl lipid A is disclosed in International Patent Publication No. WO 92/116556. 3-DMPL is an example of a substance that can enhance the TH1 over TH2 directing properties of administered allergens.